PB2506: EVIDENCE OF SPLEEN STIFFNESS PROGRESSION BY TRANSIENT ELASTOGRAPHY IN SCD PATIENTS: RESULTS FROM AN EXPLORATORY STUDY
Authors: Andrea Piolatto, Alessio Matrone, Alessandro Bisaccia, Silvia Lauria, Giovanni Ferrero, Vincenzo Voi
Journal: HemaSphere (2023)

Topic: 26. Sickle cell disease Background: Sickle Cell Disease (SCD) is a monogenic disorder resulting in the production of abnormal hemoglobin molecules. Their pathological polymerization causes aggregation of sickled red blood cells, leading to vaso-occlusive crises and multiple local or extended infarctions. Alterations of the endothelial walls and abnormal activation of inflammatory processes also contribute to these outcomes. The spleen presents peculiar structural and functional features that could promote such a process, namely the presence of a narrow microcirculation and a low-oxygen and relatively hypoxic environment. As a consequence of chronic sickling and infarctions within the spleen, progressive fibrosis, atrophy, and eventually, dysfunction of the organ are often observed in individuals with SCD. However, the biological mechanisms underlying the progression of these events and their clinical implications have been poorly investigated until now. The evaluation of Spleen Stiffness (SS) by elastography, usually paired with Liver Stiffness (LS), is an established analysis widely used in other pathologies as a marker of disease activity and progression. However, little information is available on its measurement and clinical role in SCD. Aims: This work primarily intends to evaluate the feasibility of SS assessment and obtain SS measurements in a group of SCD patients. Furthermore, we aim at investigating any association of SS with multiple clinical and biological markers of SCD. Methods: We conducted a cross-sectional, monocentric, observational study measuring LS and SS by Vibration-Controlled Transient Elastography (TE) in clinically stable SCD patients. Hematological and clinical parameters were obtained by clinical records. The study was approved by the local EC/IRB (Registration N 268/2021). Values were normalized for uni- multivariate analysis. Results: Twenty SCD patients aged 20,6 ± 13,9 participated in the study; spleen stiffness was measured in 17 (85%), in 3 (15%) patients, spleen was not recognizable. Median SS was 25,2 kPa (n=17; IQR 17,5 – 31,7; range = 10,5 - 100). Median LS was 4,7 kPa (n=20; IQR= 4,1 – 4,7; range = 3,2 -7,6). In adults, SS was higher than children (p = 0,01) with age showing a significant correlation with SS (R2 = 0,28; n (17); p = 0,03). The risk of stiffness increment was +50% per year for the spleen, and +5% per year for the liver (P=0.009). No associations with any hematological (mean Hb, MCV, HbS (%), HbF (%) or serum ferritin) or clinical parameters (hydroxyurea dose, blood units received/year, VOC events, rate of hospitalizations/year) were observed. Summary/Conclusion: Here we present a clinical evaluation of SS in SCD patients measured by noninvasive TE, showing a 10-fold increase in the risk of fibrosis progression when compared to other tissues not predominantly affected by the pathology, i.e. the liver. This result was not dependent on the adopted therapy nor on SCD severity which was assessed by the clinical and biological parameters commonly adopted to monitor this disease, in agreement with previous data. Together, these observations suggest the presence of an unbalanced process promoting progressive fibrosis in the spleen of SCD patients, which is not sufficiently inhibited by the common standards of care. Further studies should investigate the underlying pathological mechanisms and the relevance for associated clinical outcomes. Keywords: Sickle cell patient, Sickle cell disease, Spleen, Sickle cell anemia